Clinical Question

Does bedtime administration of blood pressure medications improve outcomes?

Bottom Line

In contrast with the large Hygia Chronotherapy Trial, this equally large TIME (Treatment in Morning versus Evening) study found that it does not matter when patients take their blood pressure medications. Patients should take their antihypertensive medication when it is best for them. (Level of Evidence = 2b)

Synopsis

The Hygia Chronotherapy Trial included more than 19,000 adults with hypertension and found that bedtime administration of antihypertensive medications decreased cardiovascular death and morbidity over more than six years of follow-up. However, hypertension researchers thought the results were too good to be true. An independent review of the data confirmed the original study's findings. In the TIME study, researchers randomly assigned adults with treated hypertension to take all their antihypertension medications in the morning (6 a.m. to 10 a.m.; n = 10,601) or in the evening (8 p.m. to midnight; n = 10,503). The researchers instructed the evening-dose patients who were taking a diuretic to take the diuretic earlier (6 p.m.) if they were troubled by nocturia, or in the morning if the nocturia continued. The researchers used intention-to-treat analysis to compare the rate of the primary outcome: a composite of vascular death or hospitalization for nonfatal myocardial infarction or nonfatal stroke. The researchers used patient-submitted data supplemented with data from national registries. Adjudicators masked to allocation made the final outcome determinations. A total of 90.5% of participants were White, 42.5% were women, and 12.9% had preexisting cardiovascular disease. The mean baseline characteristics of each group were balanced. After a median follow-up of 5.2 years, 3.7% of the morning-dose patients and 3.4% of the evening-dose patients experienced the endpoint, and their time to first occurrence was similar. There was no difference in the rate of any of the individual outcome components or in all-cause mortality (4.1% vs. 4.2%, respectively). The rate of adverse effects, including excessive bathroom visits (day or night; 36.4% vs. 40.0%, respectively), were similar for both groups.